Pharmacokinetics of IsavuconazolePhase 1NCT01660477
Drug-drug Interaction Study Between Lopinavir/Ritonavir and Isavuconazole
A Phase 1 study testing Isavuconazole and Lopinavir/ritonavir in people with Pharmacokinetics of Isavuconazole and Pharmacokinetics of Lopinavir/Ritonavir, run by Astellas Pharma Global Development, Inc. at 1 site in United States.
Trial summary
The purpose of this two part study is to assess the effect of multiple doses of isavuconazole on the pharmacokinetics of multiple doses of lopinavir/ritonavir and the effect of multiple doses of lopinavir/ritonavir on the pharmacokinetics of isavuconazole. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Pharmacokinetics of Isavuconazole, Pharmacokinetics of Lopinavir/Ritonavir, Healthy Volunteers
- What is being tested?
- Isavuconazole and Lopinavir/ritonavir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 68 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2012to Oct 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- The subject has a body weight of at least 45 kg and has a body mass index (BMI) of 18 to 32 kg/m2, inclusive
- Results for aspartate aminotransferase (AST) and alanine aminotransferase (ALT), total bilirubin, lipase, amylase, glucose and triglycerides must be within the normal range
- The female subject agrees to sexual abstinence, or is surgically sterile, postmenopausal (defined as at least 2 years at Screening without menses), or using a medically acceptable double barrier method (e.g. spermicide and diaphragm, or spermicide and condom) to prevent pregnancy and agrees to continue using this method from Screening until 3 weeks after the follow-up visit at the end of the study; and is not lactating or pregnant as documented by negative pregnancy tests at Screening and Day -1
- The male subject agrees to sexual abstinence, is surgically sterile, or is using a medically acceptable method to prevent pregnancy and agrees to continue using this method from Screening until 3 weeks after the follow-up visit at the end of the study
Who cannot join
- The subject has a history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmia or torsade de pointes, structural heart disease, or family history of Long QT syndrome (suggested by sudden death of a close relative at a young age due to possible or probable cardiac causes)
- The subject has a history of pancreatitis
- The subject has a positive result for hepatitis C antibodies, hepatitis B surface antigen at Screening or is known to be positive for human immunodeficiency virus (HIV)
- The subject has a known or suspected allergy to any of the components of the trial products including lopinavir/ritonavir or the azole class of compounds, or a history of multiple and/or severe allergies to drugs or foods (as judged by the investigator), or a history of severe anaphylactic reactions- - The subject is a smoker (any use of tobacco or nicotine containing products) within 6 months prior to Screening
- The subject has had treatment with prescription drugs or complementary and alternative medicines within 14 days prior to Day -1, or over-the-counter medications within 1 week prior to Day -1, with the exception of acetaminophen up to 2 g/day
- The subject has a recent history (within the last 2 years) of drug or alcohol abuse, as defined by the investigator, or a positive drug and/or alcohol screen
- The subject has participated in a previous isavuconazole study
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1, Open-Label, Parallel Study to Evaluate the Effect of Multiple Doses of Isavuconazole on the Pharmacokinetics of Multiple Doses of Lopinavir/Ritonavir and the Effects of Lopinavir/Ritonavir on the Pharmacokinetics of Multiple Doses of Isavuconazole in Healthy Adult Subjects
The purpose of this two part study is to assess the effect of multiple doses of isavuconazole on the pharmacokinetics of multiple doses of lopinavir/ritonavir and the effect of multiple doses of lopinavir/ritonavir on the pharmacokinetics of isavuconazole.
Part 1 of the study includes 12 subjects randomized to receive either isavuconazole alone or isavuconazole in combination with lopinavir/ritonavir. The purpose of Part 1 is to evaluate safety and tolerability and to establish the effect of multiple doses of lopinavir/ritonavir on isavuconazole.
Part 2, if initiated, includes 54 subjects randomized to receive isavuconazole alone, lopinavir/ritonavir alone, or isavuconazole in combination with lopinavir/ritonavir.
- Conditions
- Pharmacokinetics of Isavuconazole, Pharmacokinetics of Lopinavir/Ritonavir, Healthy Volunteers
- Being tested
- Isavuconazole, Lopinavir/ritonavir
- Keywords
- Isavuconazole, Lopinavir/ritonavir, Healthy Volunteers, BAL8557, Kaletra ®
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IsavuconazoleDrug
Also called BAL8557
oral
Lopinavir/ritonavirDrug
Also called KALETRA®
oral
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: isavuconazole only | Experimental | Isavuconazole three times per day (TID) on Days 1-2, and once daily (QD) on Days 3 thru 13 Receives: Drug: Isavuconazole |
| Arm 2 : LPV/RTV only | Experimental | Lopinavir/ritonavir (LPV/RTV) twice daily (BID) on Days 1-12 and once on Day 13 Receives: Drug: Lopinavir/ritonavir |
| Arm 3: isavuconazole and LPV/RTV | Experimental | Isavuconazole three times per day (TID) on Days 1-2, and once daily (QD) on Days 3 thru 13 in combination with lopinavir/ritonavir twice daily (BID) on Days 1-13 Receives: Drug: Isavuconazole; Drug: Lopinavir/ritonavir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetic (PK) for isavuconazole: AUCtau
(Arms 1 and 3) Area under the concentration time curve during the during time interval between consecutive dosing (AUCtau) (tau=24)
Measured: Part 1, Day 13: predose, 0.5, 1, 2, 3, 4, 6, 8,10,12,16, and 24 hours post-dose
Pharmacokinetic (PK) profile for isavuconazole: AUC tau and Cmax
(Arms 2 and 3) Maximum concentration (Cmax)
Measured: Part 2, Day 13: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hours post dose
Pharmacokinetic (PK) profile for lopinavir/ritonavir: AUC tau and Cmax
(Arms 2 and 3) AUC during time interval between consecutive dosing (AUCtau) (tau=12)
Measured: Part 2, Day 13: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours post dose
Secondary outcomes (5)
PK for isavuconazole (in plasma): trough concentration (Ctrough)
(Arms 1 and 3)
Measured: Parts 1 and 2, Days 3, 5, 7, 9 and 11: pre-dose
PK profile for isavuconazole (in plasma): Cmax, tmax
(Arms 1 and 3) Time to attain Cmax (tmax)
Measured: Parts 1 and 2, Day 13: predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12,16, and 24 hours post-dose
PK for lopinavir/ritonavir (in plasma): trough concentration (Ctrough)
(Arms 2 and 3)
Measured: Part 2, Days 3, 5, 7, 9 and 11: pre-dose
PK for lopinavir/ritonavir (in plasma): tmax
(Arms 2 and 3)
Measured: Part 2, Day 13: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours post dose
Safety and tolerability of isavuconazole alone and in combination with lopinavir (LPV) and ritonavir (RTV) assessed by recording of adverse events, physical examination, clinical laboratory evaluation, electrocardiograms (ECGs) and vital signs
Measured: Part 1, Days 1 - 20 ± 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2012 (estimated)
- Study startJun 2012
- Primary completionOct 2012
- Study completionOct 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pharmacokinetics of IsavuconazoleStudies of the same condition, open and under way.
- More trials run by Astellas Pharma Global Development, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 68 participants (actual)
Sponsor and investigators
- Lead sponsor
- Astellas Pharma Global Development, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Basilea Pharmaceutica International Ltd
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Astellas Pharma Global Development
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01660477
- Sponsor's protocol ID
- 9766-CL-0035
- Status last verified
- Feb 2015
- First submitted
- 6 Aug 2012
- Last updated
- 23 Feb 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-Label, Parallel Study to Evaluate the Effect of Multiple Doses of Isavuconazole on the Pharmacokinetics of Multiple Doses of Lopinavir/Ritonavir and the Effects of Lopinavir/Ritonavir on the Pharmacokinetics of Multiple Doses of Isavuconazole in Healthy Adult Subjects
- ClinicalTrials.gov ID
- NCT01660477
- Acronym / sponsor ID
- 9766-CL-0035
- Conditions
- Pharmacokinetics of Isavuconazole, Pharmacokinetics of Lopinavir/Ritonavir, Healthy Volunteers
- Keywords
- Isavuconazole, Lopinavir/ritonavir, Healthy Volunteers, BAL8557, Kaletra ®
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 68 participants (actual)
- Lead sponsor
- Astellas Pharma Global Development, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Basilea Pharmaceutica International Ltd
- Study start
- Jun 2012
- Primary completion
- Oct 2012 (actual)
- Study completion
- Oct 2012 (actual)
- First posted
- 8 Aug 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this two part study is to assess the effect of multiple doses of isavuconazole on the pharmacokinetics of multiple doses of lopinavir/ritonavir and the effect of multiple doses of lopinavir/ritonavir on the pharmacokinetics of isavuconazole.
Part 1 of the study includes 12 subjects randomized to receive either isavuconazole alone or isavuconazole in combination with lopinavir/ritonavir. The purpose of Part 1 is to evaluate safety and tolerability and to establish the effect of multiple doses of lopinavir/ritonavir on isavuconazole.
Part 2, if initiated, includes 54 subjects randomized to receive isavuconazole alone, lopinavir/ritonavir alone, or isavuconazole in combination with lopinavir/ritonavir.
Study design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm 1: isavuconazole only | Experimental | Drug: IsavuconazoleIsavuconazole three times per day (TID) on Days 1-2, and once daily (QD) on Days 3 thru 13 |
| Arm 2 : LPV/RTV only | Experimental | Drug: Lopinavir/ritonavirLopinavir/ritonavir (LPV/RTV) twice daily (BID) on Days 1-12 and once on Day 13 |
| Arm 3: isavuconazole and LPV/RTV | Experimental | Drug: Isavuconazole, Drug: Lopinavir/ritonavirIsavuconazole three times per day (TID) on Days 1-2, and once daily (QD) on Days 3 thru 13 in combination with lopinavir/ritonavir twice daily (BID) on Days 1-13 |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- The subject has a body weight of at least 45 kg and has a body mass index (BMI) of 18 to 32 kg/m2, inclusive
- Results for aspartate aminotransferase (AST) and alanine aminotransferase (ALT), total bilirubin, lipase, amylase, glucose and triglycerides must be within the normal range
- The female subject agrees to sexual abstinence, or is surgically sterile, postmenopausal (defined as at least 2 years at Screening without menses), or using a medically acceptable double barrier method (e.g. spermicide and diaphragm, or spermicide and condom) to prevent pregnancy and agrees to continue using this method from Screening until 3 weeks after the follow-up visit at the end of the study; and is not lactating or pregnant as documented by negative pregnancy tests at Screening and Day -1
- The male subject agrees to sexual abstinence, is surgically sterile, or is using a medically acceptable method to prevent pregnancy and agrees to continue using this method from Screening until 3 weeks after the follow-up visit at the end of the study
Key exclusion criteria (7 listed)
- The subject has a history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmia or torsade de pointes, structural heart disease, or family history of Long QT syndrome (suggested by sudden death of a close relative at a young age due to possible or probable cardiac causes)
- The subject has a history of pancreatitis
- The subject has a positive result for hepatitis C antibodies, hepatitis B surface antigen at Screening or is known to be positive for human immunodeficiency virus (HIV)
- The subject has a known or suspected allergy to any of the components of the trial products including lopinavir/ritonavir or the azole class of compounds, or a history of multiple and/or severe allergies to drugs or foods (as judged by the investigator), or a history of severe anaphylactic reactions- - The subject is a smoker (any use of tobacco or nicotine containing products) within 6 months prior to Screening
- The subject has had treatment with prescription drugs or complementary and alternative medicines within 14 days prior to Day -1, or over-the-counter medications within 1 week prior to Day -1, with the exception of acetaminophen up to 2 g/day
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IsavuconazoleAlso: BAL8557oral | Drug | Arm 1: isavuconazole only, Arm 3: isavuconazole and LPV/RTV |
| Lopinavir/ritonavirAlso: KALETRA®oral | Drug | Arm 2 : LPV/RTV only, Arm 3: isavuconazole and LPV/RTV |
Primary outcome
Pharmacokinetic (PK) for isavuconazole: AUCtau
Time frame: Part 1, Day 13: predose, 0.5, 1, 2, 3, 4, 6, 8,10,12,16, and 24 hours post-dose
(Arms 1 and 3) Area under the concentration time curve during the during time interval between consecutive dosing (AUCtau) (tau=24)
Pharmacokinetic (PK) profile for isavuconazole: AUC tau and Cmax
Time frame: Part 2, Day 13: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hours post dose
(Arms 2 and 3) Maximum concentration (Cmax)
Pharmacokinetic (PK) profile for lopinavir/ritonavir: AUC tau and Cmax
Time frame: Part 2, Day 13: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours post dose
(Arms 2 and 3) AUC during time interval between consecutive dosing (AUCtau) (tau=12)
5 secondary outcomes
PK for isavuconazole (in plasma): trough concentration (Ctrough)
Time frame: Parts 1 and 2, Days 3, 5, 7, 9 and 11: pre-dose
PK profile for isavuconazole (in plasma): Cmax, tmax
Time frame: Parts 1 and 2, Day 13: predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12,16, and 24 hours post-dose
PK for lopinavir/ritonavir (in plasma): trough concentration (Ctrough)
Time frame: Part 2, Days 3, 5, 7, 9 and 11: pre-dose
PK for lopinavir/ritonavir (in plasma): tmax
Time frame: Part 2, Day 13: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours post dose
Safety and tolerability of isavuconazole alone and in combination with lopinavir (LPV) and ritonavir (RTV) assessed by recording of adverse events, physical examination, clinical laboratory evaluation, electrocardiograms (ECGs) and vital signs
Time frame: Part 1, Days 1 - 20 ± 2
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2015.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Astellas Pharma Global Development
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Isavuconazole and Lopinavir/ritonavir in people with Pharmacokinetics of Isavuconazole and Pharmacokinetics of Lopinavir/Ritonavir, run by Astellas Pharma Global Development, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Feb 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pharmacokinetic (PK) for isavuconazole: AUCtau (time frame: Part 1, Day 13: predose, 0.5, 1, 2, 3, 4, 6, 8,10,12,16, and 24 hours post-dose). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2015.